Synthesis, Spectroscopic Characterization and Antimicrobial Activity of Some New 2-Substituted Imidazole Derivatives
Affiliation(s)
Department of Chemistry, Faculty of Science, Al-Azhar University, Girls’ Branch, Nasr City, Cairo, Egypt.
Department of Chemistry, Faculty of Science, Al-Azhar University, Girls’ Branch, Nasr City, Cairo, Egypt.
ABSTRACT
The reaction of imidazole-2-thione derivative 1 with 2-chloro-N-p-tolylacetamide afforded the corresponding 2-(1HI-imidazol-2-ylthio)-N-p-tolylacetamide 2. Reaction compound 2 with different reagents such as p-chlorobenzaldehyde and p-chlorophenyl diazonium chloride afforded the corresponding arylidene derivative 3 and hydrazone derivative 6. Reactions of 2 with carbon disulfide in dimethylformamide (DMF) in one equivalent potassium hydroxide afforded intermediate potassium sulphide salt 8, which treatment with dilute hydrochloric acid and phenacyl bromide afforded the corresponding 2-[p-tolylcarbamoyl]ethanedithioic acid 9 and 3-[benzo-ylmethylthio]-N-p-tolyl-3-thioxo-propaneamide 10. While the reaction 2 with carbon disulphide in the presence of two equivalent potassium hydroxide in DMF gave non-isolated potassium salt 11, which was allowed to react with halogenated compounds namely ethyl chloroacetate and methyl iodide afforded the corresponding 3, 3-bis[(ethoxycarbonyl)methylthio]-N-p-tolylacrylamide 12 and 3,3-bis-(methylthio)-N-p-tolylacrylamide 13 respectively. Reaction 2 with phenyl isothiocyanate in basic DMF yielded the intermediate potassium sulphide salt 18. Acidification 18 with dilute hydro-chloric acid afforded the corresponding thiocarbamoyl derivative 19. Treatment of intermediate 18 with methyl iodide, phenacyl bromide and ethylchloroacetate afforded the 3-anilino-3-(methylthio)-N-p-tolylacrylamide 20, 2-(1,3-thiazol-2(3H)-ylidene)-N-p-tolylacetamide 21 and 2-(4-oxo-3-phenyl-1,3-thiazolidin-2-ylidene)-N-p-tolylacetamide 22 respectively. The structure of the newly synthesized compounds has been confirmed by elemental analysis and spectra data. Synthesized compounds 2, 3, 6, 13, 15a, 15b, 17, 20, 21, 22 and 23 were screened for their antibacterial activities in vitro against Gram-positive (Staphylococcus aureus and Bacillus subtilis), Gram-negative (Pseudomonas aeuroginosa and Escherichia coli ) and antifungal activities against (Aspergillus fumigates, Syncephalastrum racemosum, Geotrichum candidum and Candida albicans).
The reaction of imidazole-2-thione derivative 1 with 2-chloro-N-p-tolylacetamide afforded the corresponding 2-(1HI-imidazol-2-ylthio)-N-p-tolylacetamide 2. Reaction compound 2 with different reagents such as p-chlorobenzaldehyde and p-chlorophenyl diazonium chloride afforded the corresponding arylidene derivative 3 and hydrazone derivative 6. Reactions of 2 with carbon disulfide in dimethylformamide (DMF) in one equivalent potassium hydroxide afforded intermediate potassium sulphide salt 8, which treatment with dilute hydrochloric acid and phenacyl bromide afforded the corresponding 2-[p-tolylcarbamoyl]ethanedithioic acid 9 and 3-[benzo-ylmethylthio]-N-p-tolyl-3-thioxo-propaneamide 10. While the reaction 2 with carbon disulphide in the presence of two equivalent potassium hydroxide in DMF gave non-isolated potassium salt 11, which was allowed to react with halogenated compounds namely ethyl chloroacetate and methyl iodide afforded the corresponding 3, 3-bis[(ethoxycarbonyl)methylthio]-N-p-tolylacrylamide 12 and 3,3-bis-(methylthio)-N-p-tolylacrylamide 13 respectively. Reaction 2 with phenyl isothiocyanate in basic DMF yielded the intermediate potassium sulphide salt 18. Acidification 18 with dilute hydro-chloric acid afforded the corresponding thiocarbamoyl derivative 19. Treatment of intermediate 18 with methyl iodide, phenacyl bromide and ethylchloroacetate afforded the 3-anilino-3-(methylthio)-N-p-tolylacrylamide 20, 2-(1,3-thiazol-2(3H)-ylidene)-N-p-tolylacetamide 21 and 2-(4-oxo-3-phenyl-1,3-thiazolidin-2-ylidene)-N-p-tolylacetamide 22 respectively. The structure of the newly synthesized compounds has been confirmed by elemental analysis and spectra data. Synthesized compounds 2, 3, 6, 13, 15a, 15b, 17, 20, 21, 22 and 23 were screened for their antibacterial activities in vitro against Gram-positive (Staphylococcus aureus and Bacillus subtilis), Gram-negative (Pseudomonas aeuroginosa and Escherichia coli ) and antifungal activities against (Aspergillus fumigates, Syncephalastrum racemosum, Geotrichum candidum and Candida albicans).
KEYWORDS
Imidazole-2-Thione, α-Oxoketen Dithioacetals, Thiocarbamyl, Thiazole, Antibacterial, Antifungal
Imidazole-2-Thione, α-Oxoketen Dithioacetals, Thiocarbamyl, Thiazole, Antibacterial, Antifungal
Cite this paper
Salman, A. , Abdel-Aziem, A. and Alkubbat, M. (2015) Synthesis, Spectroscopic Characterization and Antimicrobial Activity of Some New 2-Substituted Imidazole Derivatives. International Journal of Organic Chemistry, 5, 15-28. doi: 10.4236/ijoc.2015.51003.
Salman, A. , Abdel-Aziem, A. and Alkubbat, M. (2015) Synthesis, Spectroscopic Characterization and Antimicrobial Activity of Some New 2-Substituted Imidazole Derivatives. International Journal of Organic Chemistry, 5, 15-28. doi: 10.4236/ijoc.2015.51003.
References
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[1] Dieter, R.K. (1986) α-Oxo Ketene Dithioacetals and Related Compounds: Versatile Three-Carbon Synthons. Tetrahedron, 42, 3029-3096.
http://dx.doi.org/10.1016/S0040-4020(01)87376-2 [2] Junjappa, H., Ila, H. and Asokan, C.V. (1990) α-Oxoketene-S,S-, N,S- and N,N-acetals: Versatile Intermediates in Organic Synthesis. Tetrahedron, 46, 5423-5506.
http://dx.doi.org/10.1016/S0040-4020(01)87748-6 [3] Khali, M.A., Sayed, S.M. and Raslan, M.A. (2012) Reactivity of 2-Cyano-N-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)-3-(methylthio)-1-phenyl-1H-pyrazol-5-yl)acetamide: A Facile Synthesis of Pyrazole, Thiazole, 1,3,4-Thiadiazole and Polysubstituted Thiophene Derivatives. American Journal of Organic Chemistry, 2, 161-170.
http://dx.doi.org/10.5923/j.ajoc.20120206.06 [4] Abdelhamid, A.O and Afifi, M.A. (2010) Synthesis of Some New Thiazoles and Pyrazolo[1,5-a]pyrimidines Containing an Antipyrine Moiety. Synthetic Communications, 40, 1539-1550.
http://dx.doi.org/10.1080/00397910903100726 [5] Kaya, E.G., Ozbilge, H. and Albayrak, S. (2009) Determination of Effect of Gentamicin against Staphylococcus aureus by Using Microbroth Kinetic System. Ankem Derg, 23, 110-114. [6] Sofy, A.R., Hmed, A.A., Sharaf, A.M. and El-Dougdoug, K.A. (2014) Structural Changes of Pathogenic Multiple Drug Resistance Bacteria Treated with T. vulgaris Aqueous Extract. Nature and Science, 12, 83-88. [7] Caldeira, E.M., Osório, A., Oberosler, E.L., Vaitsman, D.S., Alviano, D.S. and Nojima, M.D.G. (2013) Antimicrobial and Fluoride Release Capacity of Orthodontic Bonding Materials. Journal of Applied Oral Science, 21, 327-334.
http://dx.doi.org/10.1590/1678-775720130010 [8] Shabaan, M., Taher, A. and Osman, E.O. (2011) Synthesis of Novel 3,4-Dihydroquinoxalin-2(1H)-one Derivatives. European Journal of Chemistry, 3, 365-371. [9] Voskiene, A., Mickevicius, V. and Mikulskiene, G. (2007) Synthesis and Structural Characerization of Products Condensation 4-Carboxy-1-(4-styrylcarbonylphenyl)-2-pyrrolidinones with Hydrazines. ARKIVOC: Archive for Organic Chemistry, 2007, 303-314.
http://dx.doi.org/10.3998/ark.5550190.0008.f29 [10] Mohare, R.M., Fleit, D.H. and Sakka, O.K. (2011) Novel Synthesis of Hydrazide-Hydrazone Derivatives and Their Utilization in the Synthesis of Coumarin, Pyridine, Thiazole and Thiophene Derivatives with Antitumor Activity. Molecules, 16, 16-27.
http://dx.doi.org/10.3390/molecules16010016 [11] El-Bayouki, K.A., Basyounia, W.M., Mohamed, Y.A., Aly, M.M. and Abbas, S.Y. (2011) Novel 4(3H)-Quinazolinones Containing Biologically Active Thiazole, Pyridinone and Chromene of Expected Antitumor and Antifungal Activities. European Journal of Chemistry, 2, 455-462.
http://dx.doi.org/10.5155/eurjchem.2.4.455-462.171 [12] Elgemeie, G.H., Elghandour, A.H., Ali, H.A. and Hussein, A.M. (2002) Novel 2-Thioxohydantoin Ketene Dithioacetals: Versatile Intermediates for Synthesis of Methylsulfanylimid-azo[4,5-c]pyrazole and Methylsulfanylpyrrolo[1, 2-c]imidazoles. Synthetic Communications, 32, 2245-2253.
http://dx.doi.org/10.1081/SCC-120005435 [13] Wang, Y., Dong, D., Yang, Y., Huang, J., Ouyang, Y. and Liu, Q. (2007) A Facile and Convenient One-Pot Synthesis of Polysubstituted Thiophenes from 1, 3-Dicarbonyl Compounds in Water. Tetrahedron, 63, 2724-2728.
http://dx.doi.org/10.1016/j.tet.2006.12.090 [14] Khalil, A.M., Berghot, M.A. and Goudal, M.A. (2009) Synthesis and Antibacterial Activity of Some New Heterocycles Incorporating Phthalazine. European Journal of Medicinal Chemistry, 44, 4448-4454.
http://dx.doi.org/10.1016/j.ejmech.2009.06.003 [15] Elgemeie, G.H., Elghandour, A.H. and Abd Elaziz, G.W. (2003) Novel Synthesis of Heterocyclic Ketene N,N-, N,O-, and N,S-Acetals Using Cyanoketene Dithioacetals. Synthetic Communications, 33, 1659-1664.
http://dx.doi.org/10.1081/SCC-120018927 [16] Sommena, G.L., Comelb, A. and Kirsch, G. (2005) An Easy Access to Variously Substituted Pyrroles Starting from Ketene Dithioacetals. Synthetic Communications, 35, 693-699.
http://dx.doi.org/10.1081/SCC-200050365 [17] Bondock, S., Rabie, R., Etman, H.A. and Fadda, A. (2008) Synthesis and Antimicrobial Activity of Some New Heterocycles Incorporating Antipyrine Moiety. European Journal of Medicinal Chemistry, 43, 2122-2129.
http://dx.doi.org/10.1016/j.ejmech.2007.12.009 [18] Bondock, S., Fadaly, W. and Metwally, M.A. (2010) Synthesis and Antimicrobial Activity of Some New Thiazole, Thiophene and Pyrazole Derivatives Containing Benzothiazole Moiety. European Journal of Medicinal Chemistry, 45, 3692-3701.
http://dx.doi.org/10.1016/j.ejmech.2010.05.018 [19] Rao, R.M., Reddy, G.N. and Sreeramulu, J. (2011) Synthesis of Some New Pyrazolo-Pyrazole Derivatives Containing Indoles with Antimicrobial Activity. Der Pharma Chemica, 3, 301-309.